The lung epithelium of mammals is known to contain rare solitary neuroendocrine-like cells. Presently, we have not been able to identify any known polypeptide hormones in these cells by immunohystochemical techniques and propose that these cells contain a bioactive peptide heretofore not identified in mammals. Our studies also indicate that these cells are nonproliferative and may arise by differentiation of basal cells. Hamsters treated with the carcinogen diethylnitrosamine revealed an increase in size and number of lung neuroepithelial bodies (NEBs), a second category of lung neuroendocrine-like cells. These cells could be dissociated from the lungs of treated animals and survive in short-term culture with retention of histochemical and ultrastructural characteristics of component cells of NEBs. The cultured cells could also be stained for ACTH-like immunoreactivity, a property previously observed with human bronchial carcinoids. All extracts of carcinogen-induced rodent squamous cell carcinomas and clonal subpopulations contained comparably low levels of ACTH by radioimmunoassay. Evidence of large molecular weight forms of the hormone and increased levels is of immunoreactivity following cell cluture suggests that de novo synthesis of the hormone occurs in these tumors.